What is a hyperglycemia crisis?

What is Hyperglycemic Crisis?

Hyperglycemic crisis encompasses two life-threatening acute metabolic emergencies in diabetes: diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), both characterized by severe insulin deficiency, marked hyperglycemia, and potentially fatal complications if not treated immediately. 1

Core Pathophysiology

The fundamental mechanism driving both DKA and HHS involves:

• Reduced effective insulin action combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone), leading to increased hepatic and renal glucose production and impaired peripheral glucose utilization 1, 2

• In DKA specifically: Insulin deficiency triggers uncontrolled lipolysis (release of free fatty acids from adipose tissue) and unregulated hepatic ketogenesis, producing β-hydroxybutyrate and acetoacetate, resulting in ketonemia and metabolic acidosis 1, 2

• In HHS: Residual insulin concentrations are adequate to prevent lipolysis and ketogenesis but insufficient to facilitate glucose utilization, leading to extreme hyperglycemia without significant ketoacidosis 1

Diagnostic Criteria

Diabetic Ketoacidosis (DKA)

• Blood glucose >250 mg/dL 1
• Arterial pH <7.3 1
• Bicarbonate <15 mEq/L 1
• Moderate to high ketonuria or ketonemia 1
• Critical note: Approximately 10% of DKA cases present as euglycemic DKA (glucose <200 mg/dL), particularly with SGLT2 inhibitor use, reduced food intake, pregnancy, or alcohol use 1

Hyperosmolar Hyperglycemic State (HHS)

• Blood glucose >600 mg/dL 1, 3
• Arterial pH >7.3 1
• Bicarbonate >15 mEq/L 1
• Mild or absent ketonuria/ketonemia 1
• Effective serum osmolality >320 mOsm/kg H₂O 1, 3

Important: Approximately 10% of patients present with mixed DKA-HHS features 1

Clinical Presentation

Evolution Timeline

• DKA: Typically evolves rapidly within 24 hours in type 1 diabetes or type 2 diabetes 1
• HHS: Usually develops over several days to weeks 1

Classic Symptoms

• Polyuria, polydipsia, polyphagia 4
• Weight loss, dehydration, weakness 4
• Altered mental status progressing to coma 4

DKA-Specific Features

• Abdominal pain (characteristic of DKA, not HHS) 1, 4
• Vomiting (present in up to 25% of DKA cases) 4
• Fruity breath odor 5
• Kussmaul breathing (deep, rapid respirations) 1
• Drowsiness, flushed face 5

HHS-Specific Features

• Severe dehydration 1
• Mental status changes or coma (more prominent than in DKA) 1
• Absence of Kussmaul breathing and fruity breath 3

Mortality and Prognosis

• DKA mortality: 5% in experienced centers 1
• HHS mortality: 10-20%, approximately 10 times higher than DKA 1, 3
• Prognosis worsens significantly at extremes of age, presence of coma, and hypotension 1

Common Precipitating Factors

Most Common Triggers

• Infection: Single most common precipitating cause, including gastrointestinal infections 4, 2
• Inadequate or omitted insulin doses 1, 5
• Intercurrent illness or febrile illness 1, 2
• Corticosteroid therapy 1

Medication-Related

• SGLT2 inhibitors: Now a leading cause of DKA, including euglycemic DKA, through mechanisms involving reduced insulin doses, increased glucagon levels, enhanced lipolysis, and decreased renal ketone clearance 2
• Risk factors with SGLT2 inhibitors include very-low-carbohydrate diets, prolonged fasting, dehydration, excessive alcohol intake 1

High-Risk Scenarios

• Pregnancy (up to 2% of pregnancies with pregestational diabetes complicated by DKA) 1, 2
• Elderly individuals in chronic care facilities unable to access fluids 2
• Reduced caloric intake, particularly in patients on SGLT2 inhibitors 2

Immediate Recognition Requirements

Healthcare facilities must have systems to identify 1:

• Patients with consistently elevated blood glucose
• Those with intercurrent illness
• Type 1 diabetes patients at high risk for DKA (especially with prior DKA history)
• Blood glucose results outside specified ranges (e.g., >350 mg/dL or >19.4 mmol/L requiring immediate physician notification)

Critical Management Principles

Hyperglycemic crisis requires immediate medical care to prevent complications and death 1. The mainstays of treatment include 6, 7, 8:

• Aggressive fluid resuscitation to restore circulating volume
• Continuous intravenous insulin therapy
• Electrolyte replacement (particularly potassium monitoring and replacement)
• Treatment of underlying precipitating events
• Frequent monitoring (blood glucose every 2-4 hours, electrolytes, venous pH for DKA)

Key Clinical Pitfalls

• Do not rely on nitroprusside method for ketone monitoring during DKA treatment, as it only measures acetoacetate and acetone, not β-hydroxybutyrate (the predominant ketone); direct β-hydroxybutyrate measurement is preferred 1
• Euglycemic DKA can be missed if glucose is the only criterion assessed; always check for ketones and acidosis in at-risk patients 1
• Mixed DKA-HHS presentations occur in approximately 10% of cases, requiring recognition of both conditions 1
• Hypokalemia must be excluded before initiating insulin therapy, as insulin drives potassium into cells and can cause life-threatening hypokalemia, respiratory paralysis, and ventricular arrhythmias 1, 5